Endocrine Abstracts

Adverse effects of steroid excess on bone metabolism are well established but presentation of Cushing's syndrome with metabolic bone disease is reported to be uncommon. We describe a case of Cushing's syndrome presenting with pathological fractures probably present for 8 years before diagnosis.A 33 year old nurse first sustained spontaneous stress fractures of her metatarsals in 1994, with repeated fractures occurring up to 2002. In 2001 she developed hypertension, acute l...

Medullary thyroid cancer (MTC) is rare and mainly sporadic. About ≤25% of cases are inherited from a Ret protooncogene (RET) mutation. >90% of positive mutations develop MTC, either as familial (FMTC), or as part of MEN2. Early detection and treatment of MTC with total thyroidectomy improves prognosis.In 2006, as part of a project to deliver genetics into mainstream medicine, a multidisciplinary clinic (MDC) comprising a specialist thyroid surg...

Graves' disease (GD) is an autoimmune disease of the thyroid gland with unknown aetiology thought to be caused by a complex interaction between genetic and environmental factors. To date, the HLA region on chromosome 6p21 and the CTLA-4 gene on chromosome 2q33 are thought to account for about 50% of the genetic component of GD with the remaining genetic contribution likely to be made up of many genes each exerting a small effect on predisposition to disease. A recent study (To...

The autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), are thought to be caused by complex interactions between genetic and environmental factors, which result in an organ-specific autoimmune response being directed against the thyroid gland. GD and HT, although clinically distinct, share many immunological and histological features. Several potential susceptibility genes for AITD have been investigated, although to date only the HLA an...

Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the initiation and regulation of the cytokine cascade during an inflammatory response and is, therefore, a good candidate for involvement in the development of autoimmune disease. The TNF-alpha gene has been mapped to chromosome 6p21.3 and many single nucleotide polymorphisms (SNPs) have been detected within the gene that could affect its function. The allele frequencies of these SNPs and their relationship to...

Autoimmune diseases (AIDs) have been shown to share a series of genetic susceptibility loci, including the HLA class II region, CTLA-4 and PTPN22, indicating the sharing of key pathways between diseases. Recently, the rs1801274 single nucleotide polymorphism (SNP) within the Fc gamma receptor 2a gene (FcGR2a) has been shown to be associated with several common AIDs including type 1 diabetes, rheumatoid arthritis and coeliac disease. FcGR2a is an immune mod...

Genetic variants of the HLA class II region (DRB1, DQB1 and DQA1) and CTLA-4 contribute to susceptibility to Graves' disease (GD). Whilst disease susceptibility has been mapped to a non-coding 6.1kb 3' region of CTLA-4, the primary aetiological variants within the HLA class II region remain unknown. The aims of this study were (i) determine which of the three HLA class II loci account for the primary association with GD and (ii) examine disea...

Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Differentiated thyroid cancers exhibit aneuploidy; cytogenetic studies have demonstrated the importance of genetic instability in thyroid cancer development. Pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and over-exp...

Autoimmune thyroid diseases (AITD), such as Graves' disease (GD) and autoimmune thyroiditis (AT), cluster within families and within individuals and exhibit a strong female preponderance. The type 1 diabetes Warren Repository was established between 1989 and 1996 and contains 505 families of British white Caucasian origin. Each family consists of both parents and at least two siblings with type 1 diabetes. We have examined the clinical data collected to establish the frequency...

PTTG binding factor (PBF) is a poorly characterised 22 kDa protein that is implicated in the aetiology of pituitary and thyroid tumours. Our recent investigations have attempted to discern the function of PBF in vitro. In particular, we reported that PBF can inhibit the activity of the sodium iodide symporter (NIS), which is responsible for iodide uptake into thyroid cells. However, little is known about the precise role of PBF in vivo. We have now generated a mu...